In an effort to develop a biochemical technique that could predict biologic behavior in prostate cancers in regard to hormone dependence, we have measured tissue levels of DHT in untreated and treated prostate cancer and compared these levels to values found in other tissues. The average DHT level in 16 untreated prostate cancers was 3.1 ng/g which is less than the average 5.0 ng/g found in BPH (N equals 17) but slightly more than levels of 2.1 ng/g in normal prostates from patients less than 40 yrs of age (N equals 6). Non-androgen target tissues averaged 1.1 ng/g (N equals 13). The range of DHT values in untreated prostate cancer was wide with 2/3 of the values overlapping the BPH groups and 1/3 resembling non-androgen target tissues. Retrospective correlatins of clinical responses to anti-androgen therapy with prostate cancer DHT levels prior to treatment in 5 patients with Stage D prostate cancer revealed that objective remissions were noted in 4 patients with DHT levels greater than 2.5 ng/g while no clinical response was noted in the 1 patient with a DHT level of 1.1 ng/g. Among 10 patients with prostate cancer treated with either estrogen alone, castration alone or estrogen plus castration prior to removal of prostate tissue, significant prostatic DHT levels, ranging from 2.2-6.2 ng/g were noted in 5 patients (2 on 1 mg DES alone, 1 on 12 mg/day of Tace alone, 1 castrated only and 1 on 1 mg DES daily plus castration). These results suggest inadequacy of low dose estrogen therapy in prostate cancer and in the case of castrated patients, secretion of significant amounts of adrenal cortical androgens which act as precursors for DHT in the prostate i.e., delta 4-androstenedione and DHeA. In summary, these results suggest that most prostate cancers differentiated as regards their DHT content in comparison to benign prostate tissue. Thus far, in a small number of studies, DHT levels appear to correlate with the biologic response of the cancer to anti-androgen therapy. Tissue DHT analysis in prostates from treated patients serves as a monitor for the adequacy of androgen suppression and indicates a potential important role of adrenal cortical androgens in reactivation of prostate cancer.